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अमूर्त

Mycobacterium tuberculosis Vaccination Imprints on T-Cell Dynamics Associated with Mycobacterium tuberculosis Challenge in Rhesus Monkeys

Isabelle Magalhaes, Raija K. Ahmed, Nalini Vudattu, Donata R. Sizemore, Frank Weichold, Giulia Schirru, Maria Grazia Pau, Jaap Goudsmit, Alan Thomas, Frank Verreck, Ivanela Kondova, Jan Andersson, Yasir A.W. Skeiky, Jerry Sadoff, Hans Gaines, Rigmor Thorstensson, Mats Spångberg and Markus Maeurer

Non-human primate models aid to design novel vaccine strategies. We analyzed therefore the dynamics of cellular immune responses induced by a bacille Calmette-Guérin (BCG) / recombinant BCG (rBCG, perfringolysin plus Ag85A/B, TB10.4) prime, subsequent adenoviral (Ad35 expressing Ag85A/B and TB10.4) boosts followed by a challenge with M. tuberculosis (Mtb, Erdman strain) in peripheral blood mononuclear cells from rhesus macaques. T-cell compartment mobilization was defined by CD45RA/CCR7/CD27/CD28 expression on CD4+, CD8αα+ and CD8αβ+ T-cells and functional analysis (STAT-5 phosphorylation) was carried out using multicolor flow cytometry. CD4+ as well as CD8+ T-cells showed a marked decrease in IL-7 receptor alpha-chain (IL-7Rα) expression in vaccinated animals (n=12/12) after the first adenoviral boost, but not in control animals (who received saline). BCG- and rBCG- vaccinated animals showed a dramatic decrease of precursor (CD45RA+CCR7+) and subsequent increase of activated central memory (CD45RA-CCR7+) T-cells in the CD4+, CD8αα+ and CD8αβ+ T-cell compartments 2 weeks after Mtb challenge. In contrast, this pattern was observed in control animals only 7 weeks after Mtb challenge. Expression of IL-7Rα was markedly reduced in CD4+ T-cell subsets two weeks after Mtb challenge in BCG-vaccinated animals, yet not in rBCG-vaccinated animals or control animals. These data show that vaccination profoundly shapes the dynamics of immune memory T-cells associated with Mtb infection.